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乳腺癌分子异质性与分类治疗 被引量:6

Molecular heterogeneity and subtype-specific treatments of breast cancer
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摘要 乳腺癌在组织学、流行病学和分子特性层面是一种高度异质性的疾病。目前,基于免疫组化的乳腺癌分类方法,根据雌激素受体、孕激素受体和人类表皮生长因子受体-2(HER-2)的检测结果将乳腺癌分为临床亚型,显然与基于基因表达谱的固有亚型分类不一致。这表现为临床亚型内治疗反应性和结果的异质性。异质性肿瘤细胞的存在直接反映了亚型内部(或肿瘤内)的异质性。乳腺癌的异质性,特别是亚克隆肿瘤细胞的异质性,决定了乳腺癌的最终治疗必须准确地针对特定的亚克隆肿瘤细胞群。对原发性和转移性乳腺癌分子特征的深入分析表明,遗传改变具有很大的异质性,分子发现有助于开发针对HER-2、细胞周期蛋白依赖性激酶4/6(CDK4/6)、磷脂酰肌醇-3激酶(PI3K)或涉及BRCA突变携带者的多聚腺苷二磷酸-核糖聚合酶抑制剂和免疫治疗的新的治疗方法。 Breast cancer is a highly heterogeneous disease for its histology,epidemiology,and molecular properties.The current approach immunohistochemistry-based classification of breast cancer,which categorizes this disease into clinical subtypes based on the detection of estrogen receptor,progesterone receptor,and human epidermal growth factor receptor 2(HER-2),is apparently not identical with intrinsic subtype based on gene expression profiling.This is manifested as a heterogeneity of therapeutic responses and outcomes within the clinical subtypes.The presence of heterogeneous tumor cells directly reflected the heterogeneity within the subtype(or intratumoral heterogeneity).The heterogeneity of breast cancer,especially the heterogeneity of subcloning tumor cells,determines that the ultimate treatment for breast cancer must be an accurate targeting to the specific subcloning tumor cells.In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations,molecular findings have contributed to develop new therapeutic approaches targeting HER-2,CDK4/6,PI3K,or involving poly(ADP-ribose)polymerase inhibitors for BRCA mutation carriers and immunotherapy.
作者 王硕 郑新宇 WANG Shuo;ZHENG Xin-yu(Depart-ment of Breast Surgery,the First Hospital of China Medical University,Shenyang 110001,China)
出处 《中国实用外科杂志》 CAS CSCD 北大核心 2021年第11期1238-1243,共6页 Chinese Journal of Practical Surgery
基金 中国健康促进基金会重点项目(No.CHPFRXO180301) 辽宁省重点研发计划指导项目(No.2019JH8/10300020)。
关键词 乳腺癌 分子亚型 癌症基因组学 异质性 靶向治疗 breast cancer intrinsic subtype cancer genomics heterogeneity target therapy
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